The present invention is generally related to method and apparatus for pre-hospital or initial treatment of patients experiencing a thrombotic vascular occlusion, and is more particularly directed to an emergency application of ultrasound and an agent for lysing vascular occlusions or thrombi. Importantly, the agent may not have activity for lysing vascular occlusions without application of ultrasound.
Thrombosis can cause partial or total occlusion of blood vessels which leads to a number of important cardiovascular complications, including unstable angina, acute myocardial infarction (heart attack), cerebral vascular accidents (stroke) pulmonary embolism, deep vein thrombosis and arterial thrombosis.
It is well known that acute myocardial infarction is one of the greatest causes of death in the United States, and it has been recognized that time is of the essence in successfully treating individuals undergoing acute myocardial infarction. Many hospitals and caregiving institutions have established coronary care units with trained personnel and equipment for treating a patient in the shortest time possible upon arrival. However, important time is lost during the delivery of patients to hospitals.
Removal or lysing of vascular occlusions, or clots, may be accomplished through a variety of agents such as, for example, urokinase, streptokinase, aspirin and tissue plasminogen activators, tPA. These clot dissolving agents are generally used in order to lyse clots which have formed in the coronary arteries.
These agents are typically injected into the bloodstream or organ close to the position of the clot. Unfortunately, such agents have a side effect of causing undesirable bleeding in the patient. Thus, patients who may have an ulcer or other bleeding disorder are especially difficult to treat with systemic anticoagulants. Aspirin has found wide use as a clot inhibitor, particularly with respect to clots on the arterial side of circulation. However, aspirin is used as an adjuvant agent to prevent thrombosis and has little if any effect on an established blood clot.
Ultrasound has found use in the dissolution of vascular occlusions. For example, U.S. Pat. Nos. 5,269,291, 5,318,014, 5,362,309, 5,431,662 and 5,474,531, describe intravascular ultrasonic tools for the dissolution of intravascular blockages.
More recently, transcutaneous ultrasound has been found to enhance the activity of thrombolytic agent, for example, see U.S. Pat. Nos. 5,509,896 and 5,695,460. All of the hereinabove referenced patents have been assigned to the assignee of the present application.
Thus, while it has been recognized that the use of ultrasound with an active agent enhances the activity of the agent in lysing of a vascular occlusion, other synergistic properties have not been heretofore discovered. For instance, it has been found in accordance with the present invention that ultrasound shortens the onset of thrombolysis activity of an agent such as, for example, microbubbles or tPA. Accordingly, more rapid onset of dissolution of clots results in less damage from the vascular occlusion because of more rapid opening of the blood vessel and in the restoration of tissue perfusion. In addition, the combination of certain agents and ultrasound could reduce the likelihood of excess bleeding which may significantly increase the likelihood of survival by a patient.
A method in accordance with the present invention for providing acute care treatment of a patient experiencing thrombotic vascular occlusion generally includes the steps of introducing a selected dose of an agent for acting on a vascular occlusion in the patient in order to lyse the vascular occlusion and irradiating the vascular occlusion and active agent in order to shorten onset and accelerate the effectiveness of lysing action of the agent. In view of the well known urgency of heart attack and stroke matters, i.e., cell death is directly proportional to time, it is of utmost importance to enhance the onset and accelerate the effectiveness of the active agent in lysing the vascular occlusion.
An xe2x80x9cactive agentxe2x80x9d as used herein is meant to include an agent having little or no lysing activity without ultrasound, but exhibiting lysing activity with ultrasound.
The method in accordance with the present invention applies to coronary, cerebral and peripheral vascular (venous or arterial) occlusions and it is found that the active agent may be a thrombolytic agent, anticoagulants, agents which alter blood viscosity and supply nuclei to facilitate microstreaming, cavitation agents that enhance clot disruption (e.g., Hespan, Pentaspan, an intravenous fat emulsion such as intralipid, liposyn, a microbubble medium, and an antiplatelet agent or other suitable lysing agents).
Accordingly, apparatus in accordance with the present invention, includes a self-contained mobile unit for paramedic or emergency treatment of a patient experiencing thrombotic vascular occlusion. In view of the utmost importance of availability, the apparatus includes a plurality of active agents for dissolution of vascular occlusions. A tutored paramedic or physician selects an agent based upon the indication of patient bleeding and intravenously supplies the agent to the vascular occlusion along with transcutaneously radiating the vascular occlusion.
Accordingly, one method in accordance with the present invention includes application of ultrasound transcutaneously. Under certain situations, the ultrasound may be applied intravascularly and the active agent may be introduced proximate the vascular occlusion by direct injection.